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. 2005 May;81(955):333–337. doi: 10.1136/pgmj.2004.024646

Expression of granulocyte colony stimulating factor receptor in human colorectal cancer

X Yang 1, F Liu 1, Z Xu 1, C Chen 1, X Wu 1, G Li 1, J Li 1
PMCID: PMC1743273  PMID: 15879049

Abstract

Aims: To discover if human colorectal cancer expresses granulocyte colony stimulating factor receptor (G-CSFR) and if granulocyte colony stimulating factor (G-CSF) plays an important part in the development and progression of human colorectal cancer.

Methods: Forty two specimens of colorectal cancer and normal colorectal mucosa were investigated, taken from the colon or rectum in group of colorectal cancer patients. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) technique were used to show G-CSFR expression. The relation between expression of G-CSFR and clinical or pathological factors was analysed.

Results: Immucohistochemical analyses showed that G-CSFR was expressed in the human colorectal cancer (25 of 42, 59.52%) and seemed to be up-regulated compared with the normal mucosa (14 of 42, 33.33%, p<0.001). In pronounced contrast with mostly strongly positive tumours, corresponding normal colorectal mucosa was negative or weakly positive. A significant correlation was found between G-CSFR expression and tumour stage (p = 0.001), tumour differentiation (p<0.001), but there was no significant relation between the expression of G-CSFR and the age, sex, and tumour size (p = 0.346, p = 0.686, p = 0.459). In RT-PCR, 21 of all 42 tumours had G-CSFR mRNA expression, while only 11 of 42 normal colorectal mucosa had such expression.

Conclusions: These data show that G-CSFR is commonly expressed in human colorectal cancers, thus supporting a possible role for G-CSF in colorectal cancer physiology.

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Selected References

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  1. Arat Mutlu, Arslan Onder, Gürman Günhan, Dalva Klara, Ozcan Muhit, Uğur Aynur, Ilhan Osman. The impact of granulocyte colony stimulating factor at content of donor lymphocytes collected for cellular immunotherapy. Transfus Apher Sci. 2004 Feb;30(1):9–15. doi: 10.1016/j.transci.2003.05.004. [DOI] [PubMed] [Google Scholar]
  2. Arend William P. The mode of action of cytokine inhibitors. J Rheumatol Suppl. 2002 Sep;65:16–21. [PubMed] [Google Scholar]
  3. Avalos B. R., Gasson J. C., Hedvat C., Quan S. G., Baldwin G. C., Weisbart R. H., Williams R. E., Golde D. W., DiPersio J. F. Human granulocyte colony-stimulating factor: biologic activities and receptor characterization on hematopoietic cells and small cell lung cancer cell lines. Blood. 1990 Feb 15;75(4):851–857. [PubMed] [Google Scholar]
  4. Bernard T., Gale R. E., Linch D. C. Analysis of granulocyte colony stimulating factor receptor isoforms, polymorphisms and mutations in normal haemopoietic cells and acute myeloid leukaemia blasts. Br J Haematol. 1996 Jun;93(3):527–533. doi: 10.1046/j.1365-2141.1996.d01-1696.x. [DOI] [PubMed] [Google Scholar]
  5. Bocchietto E., Guglielmetti A., Silvagno F., Taraboletti G., Pescarmona G. P., Mantovani A., Bussolino F. Proliferative and migratory responses of murine microvascular endothelial cells to granulocyte-colony-stimulating factor. J Cell Physiol. 1993 Apr;155(1):89–95. doi: 10.1002/jcp.1041550112. [DOI] [PubMed] [Google Scholar]
  6. Calatayud Sara, Warner Timothy D., Breese Emma J., Mitchell Jane A. Modulation by colony stimulating factors of human epithelial colon cancer cell apoptosis. Cytokine. 2002 Nov 24;20(4):163–167. doi: 10.1006/cyto.2002.1999. [DOI] [PubMed] [Google Scholar]
  7. Campbell C. L., Savarese D. M., Quesenberry P. J., Savarese T. M. Expression of multiple angiogenic cytokines in cultured normal human prostate epithelial cells: predominance of vascular endothelial growth factor. Int J Cancer. 1999 Mar 15;80(6):868–874. doi: 10.1002/(sici)1097-0215(19990315)80:6<868::aid-ijc12>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  8. Chakraborty Arup, Hentzen Eric R., Seo Scott M., Smith C. Wayne. Granulocyte colony-stimulating factor promotes adhesion of neutrophils. Am J Physiol Cell Physiol. 2002 Sep 18;284(1):C103–C110. doi: 10.1152/ajpcell.00165.2002. [DOI] [PubMed] [Google Scholar]
  9. Chen Song-He, Li Xin, Huang Xiao-Jun. Effect of recombinant human granulocyte colony-stimulating factor on T-lymphocyte function and the mechanism of this effect. Int J Hematol. 2004 Feb;79(2):178–184. doi: 10.1532/ijh97.a10227. [DOI] [PubMed] [Google Scholar]
  10. Corcione A., Pistoia V. B-cell-derived granulocyte-colony stimulating factor (G-CSF). Methods. 1997 Jan;11(1):143–147. doi: 10.1006/meth.1996.0398. [DOI] [PubMed] [Google Scholar]
  11. Dalton William S. The tumor microenvironment: focus on myeloma. Cancer Treat Rev. 2003 May;29 (Suppl 1):11–19. doi: 10.1016/s0305-7372(03)00077-x. [DOI] [PubMed] [Google Scholar]
  12. Dong F., Larner A. C. Activation of Akt kinase by granulocyte colony-stimulating factor (G-CSF): evidence for the role of a tyrosine kinase activity distinct from the Janus kinases. Blood. 2000 Mar 1;95(5):1656–1662. [PubMed] [Google Scholar]
  13. Dong F., van Buitenen C., Pouwels K., Hoefsloot L. H., Löwenberg B., Touw I. P. Distinct cytoplasmic regions of the human granulocyte colony-stimulating factor receptor involved in induction of proliferation and maturation. Mol Cell Biol. 1993 Dec;13(12):7774–7781. doi: 10.1128/mcb.13.12.7774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dumont Nancy, Arteaga Carlos L. The tumor microenvironment: a potential arbitrator of the tumor suppressive and promoting actions of TGFbeta. Differentiation. 2002 Dec;70(9-10):574–582. doi: 10.1046/j.1432-0436.2002.700910.x. [DOI] [PubMed] [Google Scholar]
  15. Eshel Rinat, Neumark Eran, Sagi-Assif Orit, Witz Isaac P. Receptors involved in microenvironment-driven molecular evolution of cancer cells. Semin Cancer Biol. 2002 Apr;12(2):139–147. doi: 10.1006/scbi.2001.0422. [DOI] [PubMed] [Google Scholar]
  16. Hörtner Michael, Nielsch Ulrich, Mayr Lorenz M., Johnston James A., Heinrich Peter C., Haan Serge. Suppressor of cytokine signaling-3 is recruited to the activated granulocyte-colony stimulating factor receptor and modulates its signal transduction. J Immunol. 2002 Aug 1;169(3):1219–1227. doi: 10.4049/jimmunol.169.3.1219. [DOI] [PubMed] [Google Scholar]
  17. Kaplinsky C., Trakhtenbrot L., Hardan I., Reichart M., Daniely M., Toren A., Amariglio N., Rechavi G., Izraeli S. Tetraploid myeloid cells in donors of peripheral blood stem cells treated with rhG-CSF. Bone Marrow Transplant. 2003 Jul;32(1):31–34. doi: 10.1038/sj.bmt.1703902. [DOI] [PubMed] [Google Scholar]
  18. Kikuchi T., Nakahara S., Abe T. Granulocyte colony-stimulating factor (G-CSF) production by astrocytoma cells and its effect on tumor growth. J Neurooncol. 1996 Jan;27(1):31–38. doi: 10.1007/BF00146081. [DOI] [PubMed] [Google Scholar]
  19. Kikuchi T., Nakahara S., Abe T. Granulocyte colony-stimulating factor (G-CSF) production by astrocytoma cells and its effect on tumor growth. J Neurooncol. 1996 Jan;27(1):31–38. doi: 10.1007/BF00146081. [DOI] [PubMed] [Google Scholar]
  20. Kobayashi K., Nishikawa M., Omay S. B., Toyoda H., Deguchi K., Shirakawa S. Forskolin potentiates G-CSF-induced proliferation of a murine myeloblastic leukemia cell line. Leuk Res. 1994 Feb;18(2):111–117. doi: 10.1016/0145-2126(94)90127-9. [DOI] [PubMed] [Google Scholar]
  21. Lindemann A., Riedel D., Oster W., Mertelsmann R., Herrmann F. Recombinant human granulocyte-macrophage colony-stimulating factor induces secretion of autoinhibitory monokines by U-937 cells. Eur J Immunol. 1988 Mar;18(3):369–374. doi: 10.1002/eji.1830180308. [DOI] [PubMed] [Google Scholar]
  22. Marino V. J., Sterin-Prync A. E., Carbonetto C. H., Roguin L. P. Conformational and sequential epitopes on the human granulocyte-colony stimulating factor molecule (hG-CSF) and their role in binding to human placenta receptors. Cytokine. 2001 Oct 21;16(2):41–50. doi: 10.1006/cyto.2001.0943. [DOI] [PubMed] [Google Scholar]
  23. McCracken S. A., Grant K. E., MacKenzie I. Z., Redman C. W., Mardon H. J. Gestational regulation of granulocyte-colony stimulating factor receptor expression in the human placenta. Biol Reprod. 1999 Apr;60(4):790–796. doi: 10.1095/biolreprod60.4.790. [DOI] [PubMed] [Google Scholar]
  24. McCracken S., Layton J. E., Shorter S. C., Starkey P. M., Barlow D. H., Mardon H. J. Expression of granulocyte-colony stimulating factor and its receptor is regulated during the development of the human placenta. J Endocrinol. 1996 May;149(2):249–258. doi: 10.1677/joe.0.1490249. [DOI] [PubMed] [Google Scholar]
  25. Mizuno K., Sone S., Orino E., Nii A., Ogura T. Autonomous expressions of cytokine genes by human lung cancer cells and their paracrine regulation. Jpn J Cancer Res. 1994 Feb;85(2):179–186. doi: 10.1111/j.1349-7006.1994.tb02080.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Morikawa Keiko, Morikawa Shigeru, Nakamura Masahiko, Miyawaki Toshio. Characterization of granulocyte colony-stimulating factor receptor expressed on human lymphocytes. Br J Haematol. 2002 Jul;118(1):296–304. doi: 10.1046/j.1365-2141.2002.03574.x. [DOI] [PubMed] [Google Scholar]
  27. Müller H., Nakchbandi W., Chatzissavvidis I., Valek V. Intra-arterial infusion of 5-fluorouracil plus granulocyte-macrophage colony-stimulating factor (GM-CSF) and chemoembolization with melphalan in the treatment of disseminated colorectal liver metastases. Eur J Surg Oncol. 2001 Nov;27(7):652–661. doi: 10.1053/ejso.2001.1193. [DOI] [PubMed] [Google Scholar]
  28. Natori Takeshi, Sata Masataka, Washida Miwa, Hirata Yasunobu, Nagai Ryozo, Makuuchi Masatoshi. G-CSF stimulates angiogenesis and promotes tumor growth: potential contribution of bone marrow-derived endothelial progenitor cells. Biochem Biophys Res Commun. 2002 Oct 4;297(4):1058–1061. doi: 10.1016/s0006-291x(02)02335-5. [DOI] [PubMed] [Google Scholar]
  29. Ninci E. B., Brandstetter T., Meinhold-Heerlein I., Bettendorf H., Sellin D., Bauknecht T. G-CSF receptor expression in ovarian cancer. Int J Gynecol Cancer. 2000 Jan;10(1):19–26. doi: 10.1046/j.1525-1438.2000.99076.x. [DOI] [PubMed] [Google Scholar]
  30. Quentmeier H., Zaborski M., Drexler H. G. The human bladder carcinoma cell line 5637 constitutively secretes functional cytokines. Leuk Res. 1997 Apr;21(4):343–350. doi: 10.1016/s0145-2126(96)00132-4. [DOI] [PubMed] [Google Scholar]
  31. Richards Michael K., Liu Fulu, Iwasaki Hiromi, Akashi Koichi, Link Daniel C. Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway. Blood. 2003 Jul 31;102(10):3562–3568. doi: 10.1182/blood-2003-02-0593. [DOI] [PubMed] [Google Scholar]
  32. Scheithauer W., Kornek G. V., Raderer M., Valencak J., Weinländer G., Hejna M., Haider K., Kwasny W., Depisch D. Combined irinotecan and oxaliplatin plus granulocyte colony-stimulating factor in patients with advanced fluoropyrimidine/leucovorin-pretreated colorectal cancer. J Clin Oncol. 1999 Mar;17(3):902–906. doi: 10.1200/JCO.1999.17.3.902. [DOI] [PubMed] [Google Scholar]
  33. Tachibana M., Miyakawa A., Tazaki H., Nakamura K., Kubo A., Hata J., Nishi T., Amano Y. Autocrine growth of transitional cell carcinoma of the bladder induced by granulocyte-colony stimulating factor. Cancer Res. 1995 Aug 1;55(15):3438–3443. [PubMed] [Google Scholar]
  34. Tachibana M., Miyakawa A., Uchida A., Murai M., Eguchi K., Nakamura K., Kubo A., Hata J. I. Granulocyte colony-stimulating factor receptor expression on human transitional cell carcinoma of the bladder. Br J Cancer. 1997;75(10):1489–1496. doi: 10.1038/bjc.1997.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Thacker J. D., Dedhar S., Hogge D. E. The effect of GM-CSF and G-CSF on the growth of human osteosarcoma cells in vitro and in vivo. Int J Cancer. 1994 Jan 15;56(2):236–243. doi: 10.1002/ijc.2910560216. [DOI] [PubMed] [Google Scholar]
  36. Tsuzuki H., Fujieda S., Sunaga H., Noda I., Saito H. Expression of granulocyte colony-stimulating factor receptor correlates with prognosis in oral and mesopharyngeal carcinoma. Cancer Res. 1998 Feb 15;58(4):794–800. [PubMed] [Google Scholar]
  37. Uzumaki H., Okabe T., Sasaki N., Hagiwara K., Takaku F., Tobita M., Yasukawa K., Ito S., Umezawa Y. Identification and characterization of receptors for granulocyte colony-stimulating factor on human placenta and trophoblastic cells. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9323–9326. doi: 10.1073/pnas.86.23.9323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Westphal Gabriela, Niederberger Ellen, Blum Christoph, Wollman Yoram, Knoch Tobias A., Rebel Wolfgang, Debus Jürgen, Friedrich Eckhard. Erythropoietin and G-CSF receptors in human tumor cells: expression and aspects regarding functionality. Tumori. 2002 Mar-Apr;88(2):150–159. doi: 10.1177/030089160208800214. [DOI] [PubMed] [Google Scholar]
  39. White S. M., Alarcon M. H., Tweardy D. J. Inhibition of granulocyte colony-stimulating factor-mediated myeloid maturation by low level expression of the differentiation-defective class IV granulocyte colony-stimulating factor receptor isoform. Blood. 2000 Jun 1;95(11):3335–3340. [PubMed] [Google Scholar]

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